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      "start_line": 1,
      "status": "accepted",
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      "updated_utc": null
    },
    {
      "content": "AAFP review states oral B12 2,000 mcg/day is more effective than intramuscular 1,000 mcg/day for raising B12 levels, while oral 1,000 mcg/day is equivalent to intramuscular 1,000 mcg/day; evidence strength is low/disease-oriented.",
      "content_hash": "e084b720d8bc2d4dd365390ef98774c9d1c572198e8612be87baf1afc093691a",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "end_line": 1,
      "heading": "oral dose",
      "heading_level": 2,
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      "scope": "b12_deep_10x_test",
      "source_id": "source:aafp_oral_im",
      "start_line": 1,
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    {
      "content": "Cochrane review found very low-quality evidence that oral B12 appears as safe as intramuscular B12 for B12 deficiency treatment and that better randomized trials are needed.",
      "content_hash": "f39742a29e9276d3b985ae4cbd04a4d211bf9432044ca9988275763ca065e776",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "end_line": 1,
      "heading": "oral im quality",
      "heading_level": 2,
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      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:cochrane_oral_im",
      "start_line": 1,
      "status": "accepted",
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    {
      "content": "ADA Standards of Care 2023 abridged states long-term metformin use may be associated with biochemical B12 deficiency and periodic B12 measurement should be considered.",
      "content_hash": "c32edc5237ec435962668be6b06abd974266410aa95d5afc76bfb8c8a88bf2f6",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "end_line": 1,
      "heading": "ada monitor",
      "heading_level": 2,
      "id": "chunk:ada_metformin_b12:ada_monitor",
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      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:ada_metformin_b12",
      "start_line": 1,
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    {
      "content": "BMJ review states diagnosing B12 deficiency is challenging because no single specific measurement reliably diagnoses or rules out deficiency.",
      "content_hash": "98b22a5e54a6aea8827401992e209b3c4791c94a360eefb8ac36d58f5ce1058b",
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      "end_line": 1,
      "heading": "diagnosis limits",
      "heading_level": 2,
      "id": "chunk:bmj_b12_diagnosis:diagnosis_limits",
      "meta": {},
      "profile": "supplement_research",
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      "start_line": 1,
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    {
      "content": "PubMed record for a systematic review reports serum B12 concentrations were significantly lower in patients treated with metformin than in comparison groups such as placebo or rosiglitazone.",
      "content_hash": "3e186ca8e7932c8cb39234839ada13c1095d878ee9149625cd660261acf5c554",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "end_line": 1,
      "heading": "metformin lower b12",
      "heading_level": 2,
      "id": "chunk:pubmed_metformin_review:metformin_lower_b12",
      "meta": {},
      "profile": "supplement_research",
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      "source_id": "source:pubmed_metformin_review",
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    {
      "content": "NIH ODS consumer fact sheet says B12 helps maintain blood and nerve cells and DNA synthesis; it states research has not shown one supplement form is better than others and that high-dose supplements are considered safe because only a small percentage is absorbed.",
      "content_hash": "a9cebcbb4a5abc68d004047f0a9db93865be11c7c78e5289d85b62874da9bbce",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "end_line": 1,
      "heading": "consumer safe forms",
      "heading_level": 2,
      "id": "chunk:ods_b12_consumer:consumer_safe_forms",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:ods_b12_consumer",
      "start_line": 1,
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      "token_estimate": 43,
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      "updated_utc": null
    },
    {
      "content": "PubMed metadata for diagnostic biomarkers in loop seed_pubmed_map. PMID 28925645. Title: Vitamin B12 Deficiency: Recognition and Management.. Journal: American family physician. Year: 2017. Publication types: Journal Article.",
      "content_hash": "526c9a06622f0d80e4c974ef483a5e26f23bae22f3b70776e33bb319b3f2d5ae",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
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      "heading_level": 2,
      "id": "chunk:pubmed_28925645:topic_diagnosis_biomarkers",
      "meta": {},
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      "start_line": 1,
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    {
      "content": "PubMed metadata for diagnostic biomarkers in loop seed_pubmed_map. PMID 35337631. Title: Neuropsychiatric manifestations in vitamin B12 deficiency.. Journal: Vitamins and hormones. Year: 2022. Publication types: Journal Article.",
      "content_hash": "1db4238baad69f6798e8273bafe3ddb1129e7722f6ae289c8715f000199af9d1",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
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      "heading_level": 2,
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      "source_id": "source:pubmed_35337631",
      "start_line": 1,
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      "token_estimate": 27,
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      "updated_utc": null
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    {
      "content": "PubMed metadata for diagnostic biomarkers in loop seed_pubmed_map. PMID 34046142. Title: Vitamin B12 deficiency: case report and review of literature.. Journal: The Pan African medical journal. Year: 2021. Publication types: Case Reports, Journal Article, Review.",
      "content_hash": "a34cb3d006d353130cfc161897fb195fe5da113ffd0b92e7485bd38ba13d0116",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "diagnostic biomarkers",
      "heading_level": 2,
      "id": "chunk:pubmed_34046142:topic_diagnosis_biomarkers",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_34046142",
      "start_line": 1,
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      "token_estimate": 35,
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    {
      "content": "PubMed metadata for diagnostic biomarkers in loop seed_pubmed_map. PMID 23301732. Title: Clinical practice. Vitamin B12 deficiency.. Journal: The New England journal of medicine. Year: 2013. Publication types: Journal Article, Review.",
      "content_hash": "c96c261c796f57289bdea78b366d2845fb1b54170757b7521c14ba52dec4d0cc",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "diagnostic biomarkers",
      "heading_level": 2,
      "id": "chunk:pubmed_23301732:topic_diagnosis_biomarkers",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_23301732",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 30,
      "type": "chunk",
      "updated_utc": null
    },
    {
      "content": "PubMed metadata for diagnostic biomarkers in loop seed_pubmed_map. PMID 35337628. Title: Vitamin B12 deficiency.. Journal: Vitamins and hormones. Year: 2022. Publication types: Journal Article.",
      "content_hash": "932b88f141548cd96fe31a835fb841706d481520d6216ea022ab7a9f2b7deebd",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "diagnostic biomarkers",
      "heading_level": 2,
      "id": "chunk:pubmed_35337628:topic_diagnosis_biomarkers",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_35337628",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 24,
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      "updated_utc": null
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    {
      "content": "PubMed metadata for diagnostic biomarkers in loop seed_pubmed_map. PMID 12643357. Title: Vitamin B12 deficiency.. Journal: American family physician. Year: 2003. Publication types: Journal Article, Review.",
      "content_hash": "6e2675eacb604f272acab120e3ba82d1eccb39de88ed3d3327dbb733ac21a343",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "diagnostic biomarkers",
      "heading_level": 2,
      "id": "chunk:pubmed_12643357:topic_diagnosis_biomarkers",
      "meta": {},
      "profile": "supplement_research",
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      "source_id": "source:pubmed_12643357",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 25,
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    {
      "content": "PubMed metadata for metformin and B12 status in loop seed_pubmed_map. PMID 38034222. Title: Metformin-Induced Vitamin B12 Deficiency in Patients With Type-2 Diabetes Mellitus.. Journal: Cureus. Year: 2023. Publication types: Journal Article, Review.",
      "content_hash": "874d845206b83da4782c4e2be1e37ed4ed97ef703a44111d582a883b0c0e41c2",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "metformin and B12 status",
      "heading_level": 2,
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      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_38034222",
      "start_line": 1,
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      "token_estimate": 32,
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      "updated_utc": null
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    {
      "content": "PubMed metadata for metformin and B12 status in loop seed_pubmed_map. PMID 37273250. Title: Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes.. Journal: World journal of diabetes. Year: 2023. Publication types: Journal Article, Review.",
      "content_hash": "4c71b086be09bcb2b03c64ad27b947734c1ed8d9e35770274558b7b6870d2e32",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "metformin and B12 status",
      "heading_level": 2,
      "id": "chunk:pubmed_37273250:topic_metformin",
      "meta": {},
      "profile": "supplement_research",
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      "source_id": "source:pubmed_37273250",
      "start_line": 1,
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    },
    {
      "content": "PubMed metadata for metformin and B12 status in loop seed_pubmed_map. PMID 34326945. Title: Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind.. Journal: World journal of diabetes. Year: 2021. Publication types: Journal Article, Review.",
      "content_hash": "dd69a27284b67f936ea870cac490cc38e7c5d300f7129cc61e5595172cb16069",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "metformin and B12 status",
      "heading_level": 2,
      "id": "chunk:pubmed_34326945:topic_metformin",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_34326945",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 38,
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      "updated_utc": null
    },
    {
      "content": "PubMed metadata for metformin and B12 status in loop seed_pubmed_map. PMID 35491956. Title: Metformin-induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes.. Journal: Diabetes, obesity & metabolism. Year: 2022. Publication types: Journal Article, Review.",
      "content_hash": "4344e192e7f1e8d8c2d8e9b9fab4e85890fda7ed080ec045ba1e210d824d1521",
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      "end_line": 1,
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      "heading_level": 2,
      "id": "chunk:pubmed_35491956:topic_metformin",
      "meta": {},
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      "source_id": "source:pubmed_35491956",
      "start_line": 1,
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    {
      "content": "PubMed metadata for metformin and B12 status in loop seed_pubmed_map. PMID 39233729. Title: Vitamin B12 Deficiency in Patients Taking Metformin: Pathogenesis and Recommendations.. Journal: Cureus. Year: 2024. Publication types: Journal Article, Review.",
      "content_hash": "7c6e431d202c1deb2edd83ee565e013fb464ce1bb3763bfeed01711172403df3",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "metformin and B12 status",
      "heading_level": 2,
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      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_39233729",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 32,
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    },
    {
      "content": "PubMed metadata for metformin and B12 status in loop seed_pubmed_map. PMID 35631186. Title: Vitamin B12 Deficiency in Patients with Diabetes on Metformin: Arab Countries.. Journal: Nutrients. Year: 2022. Publication types: Journal Article, Review.",
      "content_hash": "f3ba39bfa22ec9514d3be9c73f80cd1060048876592ed7eea7118079a5388100",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "metformin and B12 status",
      "heading_level": 2,
      "id": "chunk:pubmed_35631186:topic_metformin",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_35631186",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 33,
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      "updated_utc": null
    },
    {
      "content": "PubMed metadata for oral versus intramuscular B12 in loop seed_pubmed_map. PMID 29543316. Title: Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.. Journal: The Cochrane database of systematic reviews. Year: 2018. Publication types: Journal Article, Research Support, Non-U.S. Gov't, Systematic Review.",
      "content_hash": "cb66ec1e22cdea231714b217f121da6cd41b87daae3623716b734456f0f38955",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "oral versus intramuscular B12",
      "heading_level": 2,
      "id": "chunk:pubmed_29543316:topic_oral_im",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_29543316",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 43,
      "type": "chunk",
      "updated_utc": null
    },
    {
      "content": "PubMed metadata for oral versus intramuscular B12 in loop seed_pubmed_map. PMID 38231320. Title: Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis.. Journal: Irish journal of medical science. Year: 2024. Publication types: Journal Article, Systematic Review, Network Meta-Analysis.",
      "content_hash": "265f7ab5bc468582e3b0e7a013bd9fb2f921c5007ed0911c3d9cfbbd494935fa",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "oral versus intramuscular B12",
      "heading_level": 2,
      "id": "chunk:pubmed_38231320:topic_oral_im",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_38231320",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 52,
      "type": "chunk",
      "updated_utc": null
    },
    {
      "content": "PubMed metadata for oral versus intramuscular B12 in loop seed_pubmed_map. PMID 16585128. Title: Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials.. Journal: Family practice. Year: 2006. Publication types: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Systematic Review.",
      "content_hash": "3982e5a64418bdb66b1204ce6e6dc83a39666c97248b076748faa3e46fbae9b4",
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      "end_line": 1,
      "heading": "oral versus intramuscular B12",
      "heading_level": 2,
      "id": "chunk:pubmed_16585128:topic_oral_im",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_16585128",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 48,
      "type": "chunk",
      "updated_utc": null
    },
    {
      "content": "PubMed metadata for oral versus intramuscular B12 in loop seed_pubmed_map. PMID 16034940. Title: Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.. Journal: The Cochrane database of systematic reviews. Year: 2005. Publication types: Journal Article, Systematic Review.",
      "content_hash": "53d8db078f60fb9629cb0cad6cad375f231627581d80bebc0fbbd484b63bdd3c",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "oral versus intramuscular B12",
      "heading_level": 2,
      "id": "chunk:pubmed_16034940:topic_oral_im",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_16034940",
      "start_line": 1,
      "status": "accepted",
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      "updated_utc": null
    },
    {
      "content": "PubMed metadata for oral versus intramuscular B12 in loop seed_pubmed_map. PMID 40486314. Title: The Neurological Sequelae of Vitamin B12 Deficiency: A Systematic Review and Randomized Controlled Trial.. Journal: Cureus. Year: 2025. Publication types: Journal Article, Review.",
      "content_hash": "145b81ec6ca216314e3df64ae45acf75a425f2102be52a60dc71789661e10f6f",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "oral versus intramuscular B12",
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      "id": "chunk:pubmed_40486314:topic_oral_im",
      "meta": {},
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      "start_line": 1,
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    {
      "content": "PubMed metadata for oral versus intramuscular B12 in loop seed_pubmed_map. PMID 32819927. Title: Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12).. Journal: BMJ open. Year: 2020. Publication types: Journal Article, Multicenter Study, Pragmatic Clinical Trial, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Equivalence Trial.",
      "content_hash": "2d5480393d7830da9ce520366649c3f4daff367d6a81d6eb716bf1843bd33931",
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      "end_line": 1,
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      "source_id": "source:pubmed_32819927",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 57,
      "type": "chunk",
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    {
      "content": "PubMed metadata for pregnancy and perinatal outcomes in loop seed_pubmed_map. PMID 35818085. Title: Evidence based recommendations for an optimal prenatal supplement for women in the US: vitamins and related nutrients.. Journal: Maternal health, neonatology and perinatology. Year: 2022. Publication types: Journal Article, Review.",
      "content_hash": "3ae2b6eb186870fc5242cf8cc37ead639ed6df1574ef868f1323f4f28eec96c6",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "pregnancy and perinatal outcomes",
      "heading_level": 2,
      "id": "chunk:pubmed_35818085:topic_pregnancy",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_35818085",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 43,
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    {
      "content": "PubMed metadata for pregnancy and perinatal outcomes in loop seed_pubmed_map. PMID 31737547. Title: Folate supplementation for prevention of congenital heart defects and low birth weight: an update.. Journal: Cardiovascular diagnosis and therapy. Year: 2019. Publication types: Journal Article, Review.",
      "content_hash": "d52887ed0fdc0e127687924c8543a7be963d2e567640812f24afacbe5ed8e0f3",
      "created_utc": "2026-06-16T21:14:54+00:00",
      "end_line": 1,
      "heading": "pregnancy and perinatal outcomes",
      "heading_level": 2,
      "id": "chunk:pubmed_31737547:topic_pregnancy",
      "meta": {},
      "profile": "supplement_research",
      "scope": "b12_deep_10x_test",
      "source_id": "source:pubmed_31737547",
      "start_line": 1,
      "status": "accepted",
      "token_estimate": 39,
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      "content": "PubMed metadata for renal impairment MMA limits in loop method_expansion. PMID 23965230. Title: An audit of holotranscobalamin (\"Active\" B12) and methylmalonic acid assays for the assessment of vitamin B12 status: application in a mixed patient population.. Journal: Clinical biochemistry. Year: 2014. Publication types: Journal Article.",
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      "content": "PubMed metadata for diabetic neuropathy metformin B12 in loop neighbor_expansion. PMID 20061275. Title: Nutrition-related vitamin B12 deficiency in patients in Pakistan with type 2 diabetes mellitus not taking metformin.. Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. Year: 2010. Publication types: Journal Article.",
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      "rel": "maps_neuropathy_evidence_for",
      "scope": "b12_deep_10x_test",
      "src_id": "topic:diabetic_neuropathy_b12",
      "status": "candidate",
      "type": "edge",
      "updated_utc": null,
      "valid_at": null
    },
    {
      "attributes": {
        "loop": "gap_expansion",
        "query": "guideline consensus cobalamin folate disorders vitamin B12 deficiency diagnosis treatment"
      },
      "claim_ids": [
        "claim:topic:guideline_consensus"
      ],
      "confidence": "candidate",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "dst_id": "condition:B12_deficiency",
      "evidence_refs": [
        {
          "chunk_id": "chunk:pubmed_14656016:topic_guideline_consensus",
          "source_id": "source:pubmed_14656016",
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          }
        }
      ],
      "fact": "Gap loop adds PubMed records on guideline and consensus positions. (multi-loop PubMed map includes 2 records for guidelines consensus in loop gap_expansion.)",
      "id": "edge:f7fd2f48bd1518fa",
      "invalid_at": null,
      "meta": {},
      "profile": "supplement_research",
      "reference_time": null,
      "rel": "maps_guideline_evidence_for",
      "scope": "b12_deep_10x_test",
      "src_id": "topic:guideline_consensus_b12",
      "status": "candidate",
      "type": "edge",
      "updated_utc": null,
      "valid_at": null
    },
    {
      "attributes": {
        "loop": "neighbor_expansion",
        "query": "newborn screening maternal vitamin B12 deficiency methylmalonic acid infant"
      },
      "claim_ids": [
        "claim:topic:newborn_screening"
      ],
      "confidence": "candidate",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "dst_id": "condition:B12_deficiency",
      "evidence_refs": [
        {
          "chunk_id": "chunk:pubmed_36112821:topic_newborn_screening",
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          "span": {
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          }
        }
      ],
      "fact": "Neighbor loop adds PubMed records on newborn screening and maternal B12 status. (multi-loop PubMed map includes 6 records for newborn screening maternal B12 in loop neighbor_expansion.)",
      "id": "edge:327abb66045c0ee8",
      "invalid_at": null,
      "meta": {},
      "profile": "supplement_research",
      "reference_time": null,
      "rel": "maps_screening_evidence_for",
      "scope": "b12_deep_10x_test",
      "src_id": "topic:newborn_screening_b12",
      "status": "candidate",
      "type": "edge",
      "updated_utc": null,
      "valid_at": null
    },
    {
      "attributes": {
        "loop": "neighbor_expansion",
        "query": "vitamin B12 deficiency psychiatric manifestations depression psychosis"
      },
      "claim_ids": [
        "claim:topic:psychiatric"
      ],
      "confidence": "candidate",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "dst_id": "condition:neurologic_damage",
      "evidence_refs": [
        {
          "chunk_id": "chunk:pubmed_39047712:topic_psychiatric",
          "source_id": "source:pubmed_39047712",
          "span": {
            "end_line": 1,
            "quote_hash": "e74cdc29899a3dfc",
            "start_line": 1
          }
        },
        {
          "chunk_id": "chunk:pubmed_3057051:topic_psychiatric",
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          "span": {
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            "quote_hash": "e79d52458934800b",
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          }
        },
        {
          "chunk_id": "chunk:pubmed_15029091:topic_psychiatric",
          "source_id": "source:pubmed_15029091",
          "span": {
            "end_line": 1,
            "quote_hash": "2b0943207b81d481",
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          }
        },
        {
          "chunk_id": "chunk:pubmed_18178994:topic_psychiatric",
          "source_id": "source:pubmed_18178994",
          "span": {
            "end_line": 1,
            "quote_hash": "066e0a7125a5572b",
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          }
        },
        {
          "chunk_id": "chunk:pubmed_26345354:topic_psychiatric",
          "source_id": "source:pubmed_26345354",
          "span": {
            "end_line": 1,
            "quote_hash": "d473c89334309ef0",
            "start_line": 1
          }
        },
        {
          "chunk_id": "chunk:pubmed_21777723:topic_psychiatric",
          "source_id": "source:pubmed_21777723",
          "span": {
            "end_line": 1,
            "quote_hash": "ea30e91a92cc2f36",
            "start_line": 1
          }
        }
      ],
      "fact": "Neighbor loop adds PubMed records on psychiatric manifestations of B12 deficiency. (multi-loop PubMed map includes 6 records for psychiatric manifestations in loop neighbor_expansion.)",
      "id": "edge:20f703206fc147ae",
      "invalid_at": null,
      "meta": {},
      "profile": "supplement_research",
      "reference_time": null,
      "rel": "maps_neuropsychiatric_evidence_for",
      "scope": "b12_deep_10x_test",
      "src_id": "topic:psychiatric_b12",
      "status": "candidate",
      "type": "edge",
      "updated_utc": null,
      "valid_at": null
    },
    {
      "attributes": {
        "loop": "neighbor_expansion",
        "query": "vitamin B12 deficiency glossitis hyperpigmentation oral manifestations"
      },
      "claim_ids": [
        "claim:topic:skin_oral"
      ],
      "confidence": "candidate",
      "created_utc": "2026-06-16T21:13:01+00:00",
      "dst_id": "condition:B12_deficiency",
      "evidence_refs": [
        {
          "chunk_id": "chunk:pubmed_25559140:topic_skin_oral",
          "source_id": "source:pubmed_25559140",
          "span": {
            "end_line": 1,
            "quote_hash": "4fa3267ec1ddec62",
            "start_line": 1
          }
        }
      ],
      "fact": "Neighbor loop adds PubMed records on oral and skin manifestations. (multi-loop PubMed map includes 1 records for skin and oral manifestations in loop neighbor_expansion.)",
      "id": "edge:254a531a9bfe72da",
      "invalid_at": null,
      "meta": {},
      "profile": "supplement_research",
      "reference_time": null,
      "rel": "maps_clinical_manifestation_evidence_for",
      "scope": "b12_deep_10x_test",
      "src_id": "topic:skin_oral_b12",
      "status": "candidate",
      "type": "edge",
      "updated_utc": null,
      "valid_at": null
    }
  ],
  "research_loops": [
    {
      "created_utc": "2026-06-16T21:13:01+00:00",
      "id": "loop:curated_fact_spine",
      "meta": {},
      "name": "curated fact spine",
      "next_action": "expand or verify",
      "profile": "supplement_research",
      "purpose": "manual trusted guideline/review rows become accepted factual spine",
      "sample_source_ids": [],
      "scope": "b12_deep_10x_test",
      "source_count": 12,
      "stage": 0,
      "status": "accepted",
      "topic_count": 0,
      "topic_ids": [],
      "type": "research_loop",
      "updated_utc": null
    },
    {
      "created_utc": "2026-06-16T21:13:01+00:00",
      "id": "loop:seed_pubmed_map",
      "meta": {},
      "name": "seed PubMed map",
      "next_action": "expand or verify",
      "profile": "supplement_research",
      "purpose": "broad B12 topic buckets create candidate evidence-map rows",
      "sample_source_ids": [
        "source:pubmed_28925645",
        "source:pubmed_35337631",
        "source:pubmed_34046142",
        "source:pubmed_23301732",
        "source:pubmed_35337628",
        "source:pubmed_12643357",
        "source:pubmed_38034222",
        "source:pubmed_37273250"
      ],
      "scope": "b12_deep_10x_test",
      "source_count": 158,
      "stage": 1,
      "status": "accepted",
      "topic_count": 16,
      "topic_ids": [
        "topic:diagnosis_biomarkers",
        "topic:metformin_b12",
        "topic:oral_im_b12",
        "topic:pregnancy_b12",
        "topic:infant_b12",
        "topic:vegan_b12",
        "topic:older_adults_b12",
        "topic:neurologic_b12",
        "topic:anemia_b12",
        "topic:homocysteine_cvd_b12",
        "topic:acid_suppression_b12",
        "topic:bariatric_b12",
        "topic:ileal_ibd_b12",
        "topic:nitrous_b12",
        "topic:cognition_b12",
        "topic:safety_b12"
      ],
      "type": "research_loop",
      "updated_utc": null
    },
    {
      "created_utc": "2026-06-16T21:13:01+00:00",
      "id": "loop:neighbor_expansion",
      "meta": {},
      "name": "neighbor expansion",
      "next_action": "expand or verify",
      "profile": "supplement_research",
      "purpose": "graph neighbor risks and populations expand topic coverage",
      "sample_source_ids": [
        "source:pubmed_34454714",
        "source:pubmed_23774773",
        "source:pubmed_34484423",
        "source:pubmed_32053765",
        "source:pubmed_28972879",
        "source:pubmed_36476278",
        "source:pubmed_41861204",
        "source:pubmed_37664295"
      ],
      "scope": "b12_deep_10x_test",
      "source_count": 40,
      "stage": 2,
      "status": "accepted",
      "topic_count": 8,
      "topic_ids": [
        "topic:autoimmune_gastritis_b12",
        "topic:gastrectomy_b12",
        "topic:lactation_b12",
        "topic:children_vegan_b12",
        "topic:diabetic_neuropathy_b12",
        "topic:newborn_screening_b12",
        "topic:psychiatric_b12",
        "topic:skin_oral_b12"
      ],
      "type": "research_loop",
      "updated_utc": null
    },
    {
      "created_utc": "2026-06-16T21:13:01+00:00",
      "id": "loop:method_expansion",
      "meta": {},
      "name": "method expansion",
      "next_action": "full extraction and scoring",
      "profile": "supplement_research",
      "purpose": "diagnostic and treatment method variants add test/route rows",
      "sample_source_ids": [
        "source:pubmed_32089757",
        "source:pubmed_39367523",
        "source:pubmed_23884217",
        "source:pubmed_14656029",
        "source:pubmed_21593511",
        "source:pubmed_12816782",
        "source:pubmed_32707915",
        "source:pubmed_32670521"
      ],
      "scope": "b12_deep_10x_test",
      "source_count": 16,
      "stage": 3,
      "status": "accepted",
      "topic_count": 4,
      "topic_ids": [
        "topic:holotranscobalamin_b12",
        "topic:renal_mma_b12",
        "topic:sublingual_b12",
        "topic:intranasal_b12"
      ],
      "type": "research_loop",
      "updated_utc": null
    },
    {
      "created_utc": "2026-06-16T21:13:01+00:00",
      "id": "loop:gap_expansion",
      "meta": {},
      "name": "gap expansion",
      "next_action": "full extraction and scoring",
      "profile": "supplement_research",
      "purpose": "known gaps add conflict cost guideline and safety followups",
      "sample_source_ids": [
        "source:pubmed_14656016",
        "source:pubmed_42231716"
      ],
      "scope": "b12_deep_10x_test",
      "source_count": 2,
      "stage": 4,
      "status": "accepted",
      "topic_count": 4,
      "topic_ids": [
        "topic:folate_masking_b12",
        "topic:guideline_consensus_b12",
        "topic:route_cost_b12",
        "topic:adverse_effects_b12"
      ],
      "type": "research_loop",
      "updated_utc": null
    }
  ],
  "followup_jobs": [
    {
      "graph_neighbor_ids": [
        "compound:folate_B9",
        "risk:folate_masks_B12_deficiency",
        "condition:neurologic_damage"
      ],
      "id": "followup:b9-masking-conflict",
      "query_profile": "supplement_research",
      "reason": "build conflict table with modern critiques and guideline positions",
      "seed_topic": "folate B9 masking B12 deficiency"
    },
    {
      "graph_neighbor_ids": [
        "drug:metformin",
        "supplement:B12"
      ],
      "id": "followup:metformin-dose-duration",
      "query_profile": "supplement_research",
      "reason": "quantify risk by dose, duration, age, and baseline B12 status",
      "seed_topic": "metformin vitamin B12 dose duration"
    },
    {
      "graph_neighbor_ids": [
        "route:oral_B12",
        "route:intramuscular_B12"
      ],
      "id": "followup:oral-im-rct",
      "query_profile": "supplement_research",
      "reason": "extract trial tables and outcomes for route comparison",
      "seed_topic": "oral versus intramuscular vitamin B12 randomized trial"
    },
    {
      "graph_neighbor_ids": [
        "topic:bariatric_b12",
        "topic:ileal_ibd_b12",
        "condition:B12_deficiency"
      ],
      "id": "followup:bariatric-ileal",
      "query_profile": "supplement_research",
      "reason": "split malabsorption risk by surgery type and ileal disease extent",
      "seed_topic": "bariatric surgery ileal disease B12 deficiency"
    },
    {
      "graph_neighbor_ids": [
        "topic:nitrous_b12",
        "condition:neurologic_damage"
      ],
      "id": "followup:nitrous-neuro",
      "query_profile": "supplement_research",
      "reason": "extract exposure thresholds, MRI patterns, and treatment response evidence",
      "seed_topic": "nitrous oxide functional B12 deficiency neurologic injury"
    },
    {
      "graph_neighbor_ids": [
        "topic:diagnosis_biomarkers",
        "topic:metformin_b12",
        "topic:oral_im_b12",
        "topic:pregnancy_b12",
        "topic:infant_b12",
        "topic:vegan_b12",
        "topic:older_adults_b12",
        "topic:neurologic_b12",
        "topic:anemia_b12",
        "topic:homocysteine_cvd_b12",
        "topic:acid_suppression_b12",
        "topic:bariatric_b12",
        "topic:ileal_ibd_b12",
        "topic:nitrous_b12",
        "topic:cognition_b12",
        "topic:safety_b12",
        "topic:autoimmune_gastritis_b12",
        "topic:gastrectomy_b12",
        "topic:holotranscobalamin_b12",
        "topic:renal_mma_b12",
        "topic:sublingual_b12",
        "topic:intranasal_b12",
        "topic:lactation_b12",
        "topic:children_vegan_b12",
        "topic:diabetic_neuropathy_b12",
        "topic:folate_masking_b12",
        "topic:guideline_consensus_b12",
        "topic:route_cost_b12",
        "topic:newborn_screening_b12",
        "topic:psychiatric_b12",
        "topic:skin_oral_b12",
        "topic:adverse_effects_b12"
      ],
      "id": "followup:pubmed-full-extract",
      "query_profile": "supplement_research",
      "reason": "convert metadata map into abstract/full-text extracted evidence tables",
      "seed_topic": "B12 PubMed full extraction"
    },
    {
      "graph_neighbor_ids": [
        "loop:curated_fact_spine",
        "loop:seed_pubmed_map",
        "loop:neighbor_expansion",
        "loop:method_expansion",
        "loop:gap_expansion"
      ],
      "id": "followup:loop-quality",
      "query_profile": "supplement_research",
      "reason": "score each loop for duplicate studies, evidence type, and certainty gaps",
      "seed_topic": "B12 loop quality scoring"
    }
  ],
  "report": "# B12 multi-loop deep evidence map\n\nStatus: multi-loop source-map run with curated factual claims plus PubMed metadata rows. Not medical advice.\n\n## coverage\n- external sources: 228\n- PubMed sources: 216\n- research loops: 5\n- chunks: 235\n- claims: 260\n- graph edges: 42\n- evidence check: pass\n- PubMed import errors: 0\n\n## main findings\n- B12 needs are low in mcg/day terms, but deficiency risk depends strongly on absorption, diet, age, GI history, and medication exposure.\n- Evidence supports checking B12 status in symptomatic or high-risk metformin users; long-term metformin is repeatedly linked with lower B12 status.\n- Folate can improve megaloblastic anemia while neurologic harm from B12 deficiency continues, so B12 status matters before folate-only correction.\n- High-dose oral B12 is plausible for some deficiency treatment contexts, but oral-vs-IM evidence quality is limited.\n- B12 can lower homocysteine, but this does not prove cardiovascular event reduction.\n- B12 has no established UL because toxicity potential is low, yet high-dose use should still be tied to indication and clinician context.\n\n## research loops\n- 0 curated fact spine: topics=0 sources=12 next=expand or verify\n- 1 seed PubMed map: topics=16 sources=158 next=expand or verify\n- 2 neighbor expansion: topics=8 sources=40 next=expand or verify\n- 3 method expansion: topics=4 sources=16 next=full extraction and scoring\n- 4 gap expansion: topics=4 sources=2 next=full extraction and scoring\n\n## PubMed topic map\n- acid suppression: 6 records\n- autoimmune gastritis pernicious anemia: 6 records\n- bariatric surgery: 6 records\n- breast milk and lactation B12: 6 records\n- children vegan B12: 5 records\n- cognition depression: 5 records\n- diabetic neuropathy metformin B12: 6 records\n- diagnostic biomarkers: 18 records\n- gastrectomy and gastric surgery: 4 records\n- guidelines consensus: 2 records\n- high dose safety: 6 records\n- holotranscobalamin testing: 6 records\n- homocysteine and cardiovascular outcomes: 6 records\n- ileal disease and IBD: 6 records\n- infant deficiency and maternal status: 16 records\n- intranasal B12 route: 4 records\n- macrocytic megaloblastic anemia: 6 records\n- metformin and B12 status: 17 records\n- neurologic manifestations: 6 records\n- newborn screening maternal B12: 6 records\n- nitrous oxide: 6 records\n- older adults: 10 records\n- oral versus intramuscular B12: 18 records\n- pregnancy and perinatal outcomes: 11 records\n- psychiatric manifestations: 6 records\n- renal impairment MMA limits: 6 records\n- skin and oral manifestations: 1 records\n- vegan vegetarian intake: 15 records\n\n## evidence rows\n- Adults generally need 2.4 mcg/day vitamin B12; pregnancy and lactation needs are higher at 2.6 and 2.8 mcg/day. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:rda_sources confidence=high\n- Vitamin B12 is naturally found in animal foods and is also available through fortified foods. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:rda_sources confidence=high\n- Current NIH ODS review does not show superior absorption by methylcobalamin, cyanocobalamin, adenosylcobalamin, or hydroxycobalamin form. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:forms_absorption confidence=medium/high\n- High-dose B12 supplements can be safe but percentage absorption drops at large doses. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:forms_absorption confidence=high\n- B12 deficiency can cause megaloblastic anemia and neurologic symptoms; neurologic symptoms may occur without anemia. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:deficiency_neuro confidence=high\n- Older adults, pernicious anemia, GI disorders or surgery, vegan/vegetarian diets, and infants of vegan mothers are higher-risk groups for inadequate B12. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:risk_groups confidence=high\n- Metformin use can reduce B12 absorption or serum levels; higher dose, longer duration, symptoms, or risk factors strengthen the case for checking B12 status. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:safety_drugs confidence=high\n- Gastric acid inhibitors such as PPIs and H2 blockers can interfere with absorption of B12 from food and may contribute to deficiency. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:safety_drugs confidence=medium/high\n- High folate intake can correct B12-related megaloblastic anemia without correcting neurologic damage, potentially masking B12 deficiency. evidence=source:nih_ods_folate_hp/chunk:nih_ods_folate_hp:folate_masking confidence=high\n- When B12 and folate deficiency coexist, B12 replacement should come first to reduce neurologic risk. evidence=source:aafp_b12_recognition/chunk:aafp_b12_recognition:replace_first confidence=medium/high\n- High-dose oral B12 can raise levels and may be comparable to intramuscular treatment for some deficiency cases, but evidence quality is low or very low. evidence=source:aafp_oral_im/chunk:aafp_oral_im:oral_dose confidence=medium\n- No tolerable upper intake level has been established for B12 because toxicity potential is low. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:safety_drugs confidence=high\n- B12 can lower homocysteine as part of B-vitamin metabolism, but trials/reviews do not show cardiovascular event prevention from B12/B-vitamin supplementation. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:homocysteine_cvd_energy confidence=high\n- B12 supplementation does not appear to improve energy, endurance, or athletic performance when B12 status is already sufficient. evidence=source:nih_ods_b12_hp/chunk:nih_ods_b12_hp:homocysteine_cvd_energy confidence=medium/high\n- B12 deficiency diagnosis is not reducible to one perfect test; source reviews emphasize diagnostic uncertainty and context. evidence=source:bmj_b12_diagnosis/chunk:bmj_b12_diagnosis:diagnosis_limits confidence=medium\n- People who could become pregnant, especially with vegan diets, are highlighted for multivitamin support containing B12 and folic acid; pregnancy/lactation needs are higher. evidence=source:bc_b12_folate_guideline/chunk:bc_b12_folate_guideline:pregnancy_vegan confidence=medium/high\n- multi-loop PubMed map includes 18 records for diagnostic biomarkers in loop seed_pubmed_map. evidence=source:pubmed_28925645/chunk:pubmed_28925645:topic_diagnosis_biomarkers confidence=candidate\n- multi-loop PubMed map includes 17 records for metformin and B12 status in loop seed_pubmed_map. evidence=source:pubmed_38034222/chunk:pubmed_38034222:topic_metformin confidence=candidate\n- multi-loop PubMed map includes 18 records for oral versus intramuscular B12 in loop seed_pubmed_map. evidence=source:pubmed_29543316/chunk:pubmed_29543316:topic_oral_im confidence=candidate\n- multi-loop PubMed map includes 11 records for pregnancy and perinatal outcomes in loop seed_pubmed_map. evidence=source:pubmed_35818085/chunk:pubmed_35818085:topic_pregnancy confidence=candidate\n- multi-loop PubMed map includes 16 records for infant deficiency and maternal status in loop seed_pubmed_map. evidence=source:pubmed_30845641/chunk:pubmed_30845641:topic_infant confidence=candidate\n- multi-loop PubMed map includes 15 records for vegan vegetarian intake in loop seed_pubmed_map. evidence=source:pubmed_38987872/chunk:pubmed_38987872:topic_vegan confidence=candidate\n- multi-loop PubMed map includes 10 records for older adults in loop seed_pubmed_map. evidence=source:pubmed_31641726/chunk:pubmed_31641726:topic_older confidence=candidate\n- multi-loop PubMed map includes 6 records for neurologic manifestations in loop seed_pubmed_map. evidence=source:pubmed_38574212/chunk:pubmed_38574212:topic_neuro confidence=candidate\n- multi-loop PubMed map includes 6 records for macrocytic megaloblastic anemia in loop seed_pubmed_map. evidence=source:pubmed_32127439/chunk:pubmed_32127439:topic_anemia confidence=candidate\n- multi-loop PubMed map includes 6 records for homocysteine and cardiovascular outcomes in loop seed_pubmed_map. evidence=source:pubmed_36170884/chunk:pubmed_36170884:topic_homocysteine confidence=candidate\n- multi-loop PubMed map includes 6 records for acid suppression in loop seed_pubmed_map. evidence=source:pubmed_37060552/chunk:pubmed_37060552:topic_ppi confidence=candidate\n- multi-loop PubMed map includes 6 records for bariatric surgery in loop seed_pubmed_map. evidence=source:pubmed_34302218/chunk:pubmed_34302218:topic_bariatric confidence=candidate\n- multi-loop PubMed map includes 6 records for ileal disease and IBD in loop seed_pubmed_map. evidence=source:pubmed_38276922/chunk:pubmed_38276922:topic_ibd confidence=candidate\n- multi-loop PubMed map includes 6 records for nitrous oxide in loop seed_pubmed_map. evidence=source:pubmed_34348072/chunk:pubmed_34348072:topic_nitrous confidence=candidate\n- multi-loop PubMed map includes 5 records for cognition depression in loop seed_pubmed_map. evidence=source:pubmed_33809274/chunk:pubmed_33809274:topic_cognition confidence=candidate\n- multi-loop PubMed map includes 6 records for high dose safety in loop seed_pubmed_map. evidence=source:pubmed_30022794/chunk:pubmed_30022794:topic_safety confidence=candidate\n- multi-loop PubMed map includes 6 records for autoimmune gastritis pernicious anemia in loop neighbor_expansion. evidence=source:pubmed_34454714/chunk:pubmed_34454714:topic_autoimmune_gastritis confidence=candidate\n- multi-loop PubMed map includes 4 records for gastrectomy and gastric surgery in loop neighbor_expansion. evidence=source:pubmed_41861204/chunk:pubmed_41861204:topic_gastrectomy confidence=candidate\n- multi-loop PubMed map includes 6 records for holotranscobalamin testing in loop method_expansion. evidence=source:pubmed_32089757/chunk:pubmed_32089757:topic_holotranscobalamin confidence=candidate\n- multi-loop PubMed map includes 6 records for renal impairment MMA limits in loop method_expansion. evidence=source:pubmed_32707915/chunk:pubmed_32707915:topic_renal_mma confidence=candidate\n- multi-loop PubMed map includes 4 records for intranasal B12 route in loop method_expansion. evidence=source:pubmed_10369631/chunk:pubmed_10369631:topic_intranasal confidence=candidate\n- multi-loop PubMed map includes 6 records for breast milk and lactation B12 in loop neighbor_expansion. evidence=source:pubmed_38276540/chunk:pubmed_38276540:topic_breast_milk confidence=candidate\n- multi-loop PubMed map includes 5 records for children vegan B12 in loop neighbor_expansion. evidence=source:pubmed_21664980/chunk:pubmed_21664980:topic_children_vegan confidence=candidate\n- multi-loop PubMed map includes 6 records for diabetic neuropathy metformin B12 in loop neighbor_expansion. evidence=source:pubmed_37187650/chunk:pubmed_37187650:topic_diabetic_neuropathy confidence=candidate\n- multi-loop PubMed map includes 2 records for guidelines consensus in loop gap_expansion. evidence=source:pubmed_14656016/chunk:pubmed_14656016:topic_guideline_consensus confidence=candidate\n- multi-loop PubMed map includes 6 records for newborn screening maternal B12 in loop neighbor_expansion. evidence=source:pubmed_36112821/chunk:pubmed_36112821:topic_newborn_screening confidence=candidate\n- multi-loop PubMed map includes 6 records for psychiatric manifestations in loop neighbor_expansion. evidence=source:pubmed_39047712/chunk:pubmed_39047712:topic_psychiatric confidence=candidate\n- multi-loop PubMed map includes 1 records for skin and oral manifestations in loop neighbor_expansion. evidence=source:pubmed_25559140/chunk:pubmed_25559140:topic_skin_oral confidence=candidate\n",
  "gaps": "# gaps\n\n- This is a 10x source-map test, not a complete systematic review.\n- PubMed rows are metadata/evidence-map rows; medical conclusions still require abstract/full-text extraction and critical appraisal.\n- Need direct trial tables for oral, sublingual, and intramuscular B12 routes.\n- Need quantitative tables for metformin dose/duration, bariatric surgery, ileal disease, acid suppression, and nitrous oxide exposure.\n- Need conflict table for high folate masking versus modern critiques and NICE 2024 implementation concerns.\n- Need duplicate-study detection across systematic reviews, RCTs, cohort studies, and case reports.\n- Need risk-of-bias scoring and outcome-specific certainty labels before production use.\n"
}